IEMbase 0287: GM2A-related GM2 activator protein deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 287 |
| Nosology | 20.1.07.01 |
| Gene | GM2A |
| External IDs | OMIM:272750; ORPHA:309246 |
| Generated mapping | MAPPED; Tay-Sachs_Disease_AB_Variant.yaml |
| Candidate DisMech targets | Tay-Sachs_Disease_AB_Variant.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents GM2 gangliosidosis AB variant / hexosaminidase activator deficiency due to GM2A. Inheritance is autosomal recessive and treatability is unknown.
The clinical rows are sparse but neurologically focused: muscular hypotonia, psychiatric disturbances, spasticity, and urinary incontinence. Biochemical rows list normal-to-increased beta-hexosaminidase A activity and increased urinary oligosaccharides, consistent with a cofactor defect rather than a primary HEXA or HEXB catalytic-subunit deficiency.
DisMech phenotype coverage
Tay-Sachs_Disease_AB_Variant.yaml is the correct local target. The DisMech
entry models GM2A loss, absence of the GM2 activator protein, preserved
hexosaminidase A and B catalytic activity, failure of GM2 presentation to
hexosaminidase A, and neuronal GM2 storage.
Local phenotypes include developmental regression, cherry-red spot of the macula, neurodegeneration, nystagmus, hypotonia, and hyperacusis. Local treatment coverage is supportive care. Genetic coverage correctly uses GM2A.
Concordance and completeness
Judgement: correct mapping to Tay-Sachs_Disease_AB_Variant.yaml.
IEMbase and DisMech agree on GM2A identity, autosomal recessive inheritance, a GM2 activator/cofactor defect, hypotonia, and the important distinction from HEXA/HEXB disease: beta-hexosaminidase catalytic activity is not the primary defect. DisMech is stronger for mechanism and classic neuro-ophthalmic phenotypes. IEMbase is thinner overall but adds spasticity, urinary incontinence, psychiatric disturbance, and urinary oligosaccharide rows as review prompts.
The normal-to-increased beta-hexosaminidase A row is especially useful because it helps distinguish AB variant disease from classic Tay-Sachs, where Hex A activity is decreased.
Curation actions
- Keep this record mapped to
Tay-Sachs_Disease_AB_Variant.yaml. - Consider adding an explicit biochemical/diagnostic row for preserved Hex A/B catalytic activity if supported by local evidence sources.
- Review spasticity, urinary incontinence, psychiatric disturbance, and urinary oligosaccharides before importing them locally.